Updates on the Treatment of Diabetic Eye Disease

By Dr Nicola Gan, Consultant, Vitreo-retinal Service, National Healthcare Group Eye Institute, Tan Tock Seng Hospital

The NHG Eye Institute at TTSH continues to address the increasing demand for eye care services, with active participation in ophthalmic research and training.

The Institute provides services in the entire spectrum of ophthalmic sub-specialities and delivers quality primary and tertiary eye care to patients in Singapore and the region. In part four of the ‘Eye Discoveries’ series by the NHG Eye Institute, we take a look at recent global trends in the treatment of Diabetes related eye disease.

Diabetes mellitus is a growing health problem. Recent global estimates show that 415 million people have been diagnosed with the disease1. In 2010, 2.5% of the 32.4 million people who were certified blind and 1.9% of the 191 million people with visual impairment worldwide were attributed to diabetic retinopathy, with an increase in numbers since 19902. The main causes of loss of vision in diabetic eye disease Figure 1 – (a) Optos® wide-field fundus photo of right eye with tractional retinal detachment involving the disc and nasal retina and vitreous haemorrhage obscuring details of the rest of the fundus (b) Left eye with high risk PDR – neovascularisation of the disc and retina with pre-retinal and vitreous haemorrhage (c) Optos® wide-field intravenous fluorescein angiography of the right eye showing leakage from retinal neovascular fronds in detached retina (yellow arrows) (d) Left eye with diffuse capillary dropout (blue arrows) and leaking retinal neovascular fronds around the disc (yellow arrows). include high-risk proliferative diabetic retinopathy (PDR) with tractional retinal detachment, vitreous haemorrhage, diabetic macular edema (DME) and macular ischaemia.

Diabetic Retinopathy (DR)

DR is an end-organ microangiopathy and a marker that other end-organ complications such as diabetic nephropathy or peripheral neuropathy may also be present. The severity of DR varies, ranging from non-proliferative (mild, moderate, severe) to proliferative (low-risk, high-risk) disease. In non-proliferative DR, patients are mostly asymptomatic and fundus features include retinal microaneurysms, intraretinal haemorrhages and hard exudates. By the time patients are symptomatic, DR is usually in the proliferative stage with optic disc and retinal neovascularisation and complications including vitreous haemorrhage and tractional retinal detachment. In these cases, patients may complain of a sudden onset of floaters from vitreous haemorrhage, or progressive blurring of vision as the macula becomes involved. The gold standard of treatment for PDR is pan retinal laser photocoagulation to reduce the risk of severe vision loss3. In patients with high-risk PDR with tractional retinal detachment involving the macula or non-clearing vitreous haemorrhage, vitrectomy surgery is indicated.

Paradigm shift in the treatment of Diabetic Macular Edema (DME)

Five years ago, clinically significant diabetic macular edema was mainly treated by macular focal or grid laser photocoagulation, which was the gold standard of treatment for two decades4. However, laser photocoagulation cannot be used to treat DME involving the foveal centre, as laser scars close to the foveal centre permanently impair central vision. With the advent of multiple international large randomized controlled trials, intravitreal injections of antivascular endothelial growth factor (anti-VEGF) has become an important advance in the treatment of centre-involved DME5. FDA approved drugs include Lucentis® (ranibizumab) and Eylea® (aflibercept). A cheaper option is Avastin® (bevacizumab) which has been used off-label to treat DME worldwide. In certain patients, intravitreal steroid injections are also a suitable option but with increased risks of intraocular pressure rise and cataract formation. Different treatment protocols have been adopted by retina specialists including monthly injections, monthly monitoring visits with pro-re-nata injections or a treat-and-extend regimen.

The severity of DME and treatment response can be closely monitored with clinical examination and OCT (optical coherence tomography) scans at each visit. These highresolution laser interferometry scans show a cross-section of the macula and any intra-retinal fluid present.

Personalising treatment by tailoring treatment intervals to the individual’s response is the key to successfully treating DME. Recent studies on anti-VEGF injections for centre-involved DME have shown that the first 3 years are the most important, with a decline in the frequency of treatment needed thereafter6.

Currently, the role of macular focal or grid laser photocoagulation still exists for patients with clinically significant macular edema which does not involve the fovea7. New lasers on the market include subthreshold micropulse diode lasers that can treat even foveal-involving DME due to the enhanced duty cycle technology that minimises macular damage8. However, this has not been adopted in many centres worldwide, as larger randomised controlled trials are still lacking.

Systemic control - Optimising care of patients with diabetic eye disease

Eye screening should be performed upon diagnosis of diabetes mellitus, and at least annually thereafter if no diabetic eye disease is found, or more frequently if DR or DME is present. In patients with diabetic eye disease, intensive control of all vascular risk factors including glycaemic control9, cholesterol levels10 and blood pressure11 are essential to reduce the progression of DR. Education on the importance of regular exercise, a healthy balanced diet and compliance with family physician and ophthalmology check-ups is critical in empowering patients to take control of their own well-being. Teaching patients to keep track of their HbA1c levels as a gauge of diabetes control is helpful in involving patients in their own health care.

Communication between the family physician and ophthalmologist is important to ensure holistic care. Patients must be advised that an annual eye screen is essential even if glycaemic control is excellent. DR screening may be in the form of diabetic retinal photography (DRP) screening or a visit to the ophthalmologist. Currently, family doctors may refer patients to polyclinics or Community Health Centres for DRP screening. A fundus photo is taken and the photo is assessed by family doctors or sent to ophthalmologists in the public hospitals for grading through the national SiDRP (Singapore Integrated Diabetic Retinopathy Programme) system. The NHG Eye Institute at TTSH actively participates in this programme. Patients who are found to have features suggestive of DR, DME or other retinal problems will be referred to an ophthalmologist for further evaluation.

Learning points

Blindness from diabetic eye disease is preventable. A recent epidemiological review found a decline in the incidence of blindness due to DR in developed countries, with DME overtaking PDR as the increasingly common cause of visual impairment2. Annual eye screenings are essential for all diabetics, and early referrals to an ophthalmologist for assessment and treatment before the onset of irreversible visual impairment is crucial for all patients with suspected diabetic eye disease. Optimisation of vascular risk factors and patient education are important areas in which the family physician can work on, in a collaborative effort to reduce the growing burden from diabetic eye disease.


References

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  2. Global estimates on the number of people blind or visually impaired by diabetic retinopathy: a metaanalysis from 1990 to 2010. Diabetes Care 2016; Sep 39(9): 1643-9.
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  6. Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Arch Ophthalmol 1985; 103:1796- 806.
  7. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. The Diabetic retinopathy clinical research network. Ophthalmol 2010; Jun 117(6);1064-77.e35.
  8. Intravitreal ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: 5-year randomized trial results. Ophthalmol 2015; 122:375-81.
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  10. Sub-threshold micro-pulse diode laser treatment in diabetic macular edema: a meta-analysis of randomized controlled trials. Int J Ophthalmol 2015; 9(7): 1020-7.
  11. The effect of intensive therapy of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus: the Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329(14):977-986.
  12. Effect of medical therapies on retinopathy progression in type 2 diabetes. The Accord Study Group and Accord Eye Study Group. N Engl J Med 2010;Jul 15;363(3):233-44.
  13. Risks of progression of retinopathy and vision loss related to tight blood pressure control in type 2 diabetes mellitus. UKPDS 69, UK Prospective Diabetes Study Group. Arch Ophthalmol 2004;122:1631-40.